Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes

Substance P (SP) is a potent modulator of neuroimmunoregulation. We recently reported that human immune cells express SP and its receptor. We have now investigated the possible role that SP and its receptor plays in HIV infection of human mononuclear phagocytes. SP enhanced HIV replication in human blood-isolated mononuclear phagocytes, whereas the nonpeptide SP antagonist (CP-96,345) potently inhibited HIV infectivity of these cells in a concentration-dependent fashion. CP-96,345 prevented the formation of typical giant syncytia induced by HIV Bal strain replication in these cells. This inhibitory effect of CP-96,345 was because of the antagonism of neurokinin-1 receptor, a primary SP receptor. Both CP-96,345 and anti-SP antibody inhibited SP-enhanced HIV replication in monocyte-derived macrophages (MDM). Among HIV strains tested (both prototype and primary isolates), only the R5 strains (Bal, ADA, BL-6, and CSF-6) that use the CCR5 coreceptor for entry into MDM were significantly inhibited by CP-96,345; in contrast, the X4 strain (UG024), which uses CXCR4 as its coreceptor, was not inhibited. In addition, the M-tropic ADA (CCR5-dependent)-pseudotyped HIV infection of MDM was markedly inhibited by CP-96,345, whereas murine leukemia virus-pseudotyped HIV was not affected, indicating that the major effect of CP-96,345 is regulated by Env-determined early events in HIV infection of MDM. CP-96,345 significantly down-regulated CCR5 expression in MDM at both protein and mRNA levels. Thus, SP–neurokinin-1 receptor interaction may play an important role in the regulation of CCR5 expression in MDM, affecting the R5 HIV strain infection of MDM.

Hybrid characteristics of oligonucleotides consisting of isonucleoside 2′,5′-anhydro-3′-deoxy-3′-(thymin-1-yl)-d-mannitol with different linkage modes

Oligonucleotides consisting of the isonucleoside repeating unit 2′,5′-anhydro-3′-deoxy-3′-(thymin-1-yl)-d-mannitol (4) were synthesized with the monomeric unit 4 incorporated into oligonucleotides as 1′→4′ linkage 4a (oligomer I) or 6′→4′ linkage 4b (oligomer II). The hybrid properties of the two oligonucleotides I and II with their complementary strands were investigated by thermal denaturation and CD spectra. Oligonucleotide I (4a) formed a stable duplex with d(A)14 with a slightly reduced Tm value of 36.6°C, relative to 38.2°C for the control duplex d(T)14/d(A)14, but oligomer II (4b) failed to hybridize with a DNA complementary single strand. The spectrum of the duplex oligomer I/d(A)14 showed a positive CD band at 217 nm and a negative CD band at 248 nm attributable to a B-like conformation. Molecular modeling showed that in the case of oligomer I the C6′ hydroxy group of each unit could be located in the groove area when hybridized to the DNA single strand, which might contribute additional hydrogen bonding to the stability of duplex formation.

Molecular cytogenetic delineation of a novel critical genomic region in chromosome bands 11q22.3-923.1 in lymphoproliferative disorders.

Aberrations of the long arm of chromosome 11 are among the most common chromosome abnormalities in lymphoproliferative disorders (LPD). Translocations involving BCL1 at 11q13 are strongly associated with mantle cell lymphoma. other nonrandom aberrations, especially deletions and, less frequently, translocations, involving bands 11q21-923 have been identified by chromosome banding analysis. To date, the critical genomic segment and candidate genes involved in these deletions have not been identified. In the present study, we have analyzed tumors from 43 patients with LPD (B-cell chronic lymphocytic leukemia, n = 40; mantle cell lymphoma, n = 3) showing aberrations of bands 11q21-923 by fluorescence in situ hybridization. As probes we used Alu-PCR products from 17 yeast artificial chromosome clones spanning chromosome bands 11q14.3-923.3, including a panel of yeast artificial chromosome clones recognizing a contiguous genomic DNA fragment of approximately 9-10 Mb in bands 11q22.3-923.3. In the 41 tumors exhibiting deletions, we identified a commonly deleted segment in band 11q22.3-923.1; this region is approximately 2-3 Mb in size and contains the genes coding for ATM (ataxia telangiectasia mutated), RDX (radixin), and FDX1 (ferredoxin 1). Furthermore, two translocation break-points were localized to a 1.8-Mb genomic fragment contained within the commonly deleted segment. Thus, we have identified a single critical region of 2-3 Mb in size in which 11q14-923 aberrations in LPD cluster. This provides the basis for the identification of the gene(s) at 11q22.3-923.1 that are involved in the pathogenesis of LPD.

The evolutionary paths among galaxy types on the red sequence at 0.3 < Z < 1.5

We have studied the main evolutionary paths among the galaxy types residing on the massive end of the Red Sequence and nearby locations on the Green Valley during the last ∼9 Gyr. The morphological and star formation properties of a sample of these galaxies at 0 . 3 < z < 1 .5 with stellar masses M_∗ > 5 × 10^10 M_⊙ have been analysed. We present direct observational evidence for the first time of the existence of two main evolutionary paths among the different red galaxy types since z ∼ 1 .5, which provide some clues on the nature of the processes that have governed the assembly of present-day massive quiescent galaxies. The results are in excellent agreement with the hierarchical evolutionary framework proposed in the Eliche-Moral et al. (2010) model. Data from SHARDS (one of the ESO/GTC Large Programmes approved in 2009A) will complement and improve the present findings, shedding some light into many of the still unsettled questions concerning the migration of galaxies from the Blue Cloud to the Red Sequence at z < 1 .5.

X-ray absorption study of the ferromagnetic Cu moment at the YBa_(2)Cu_(3)O_(7)/La_(2/3)Ca_(1/3)MnO_(3) interface and variation of its exchange interaction with the Mn moment

With x-ray absorption spectroscopy and polarized neutron reflectometry we studied how the magnetic proximity effect at the interface between the cuprate high-TC superconductor YBa_(2)Cu_(3)O_(7) (YBCO) and the ferromagnet La_(2/3)Ca_(1/3)MnO_(3) (LCMO) is related to the electronic and magnetic properties of the LCMO layers. In particular, we explored how the magnitude of the ferromagnetic Cu moment on the YBCO side depends on the strength of the antiferromagnetic (AF) exchange coupling with the Mn moment on the LCMO side. We found that the Cu moment remains sizable if the AF coupling with the Mn moments is strongly reduced or even entirely suppressed. The ferromagnetic order of the Cu moments thus seems to be intrinsic to the interfacial CuO_(2) planes and related to a weakly ferromagnetic intraplanar exchange interaction. The latter is discussed in terms of the partial occupation of the Cu 3d_(3z^(2)−r^(2)) orbitals, which occurs in the context of the so-called orbital reconstruction of the interfacial Cu ions.

Tema 3, parte 1: Introducción a Javascript. Manejo de eventos

En esta presentación se introduce el lenguaje JavaScript, su uso en la web y la gestión de eventos.

Sistemas y Procesos en Publicidad y Relaciones Públicas. Tema 3, parte 1 (curso 2011-2012)

Resumen del Tema 3 (parte 1), para los grupos 1,2,3 y 4.